The human body has the ability to develop extremely powerful specific immunity against individual invading agents such as lethal bacteria, viruses, toxins, etc. This ability is typically referred to as acquired immunity. In general, two basic but closely allied types of acquired immunity occur in the body. In one type, the body develops circulating antibodies (referred to as bursal, or B lymphocytes), which are globulin molecules that are capable of attacking an invading agent. This type of acquired immunity is referred to as humoral immunity. The other type of acquired immunity is achieved through the formation of large numbers of activated lymphocytes (referred to as thymic, or T lymphocytes or T cells) that are specifically designed to destroy a foreign agent. This type of immunity is called cell-mediated immunity.
Upon exposure to particular antigens, T lymphocytes of the lymphoid tissue proliferate and release large numbers of activated T cells. These T cells pass into the circulation and are distributed throughout the body, passing through the capillary walls into the tissue spaces, back into the lymph and blood once again, and circulating again and again throughout the body, sometimes lasting for month or even years. In addition, T lymphocyte memory cells are formed and preserved in the lymphoid tissue and become additional T lymphocytes of that specific clone. These additional T lymphocytes can spread throughout the lymphoid tissue of the body, and, on subsequent exposure to the same antigen, the release of activated T cells can occur far more rapidly and much more powerfully than in a first response.
Cytotoxic T cells are direct attack cells that are capable of killing microorganisms and the body's own cells and, thus, are often referred to as “killer” cells. In general, the receptor proteins on the surfaces of the cytotoxic cells cause them to bind tightly to those organisms or cells that contain their binding-specific antigen. In the instance of the Human Immunodeficiency Virus (HIV), the immune system of the infected human produces killer T-cells that recognize epitopes (patterns of 8-11 amino acids) on the surface of T cells infected by HIV and bind thereto. The immediate affect of the binding is swelling of the T cell and release of cytotoxic substances into the attacked cell with eventual destruction of the cell. Cytotoxic T cells are especially lethal to tissue cells that have been invaded by viruses since many virus particles become entrapped in the membranes of these cells and attract the T cells due to viral antigenicity.
Through exposure to pathogen or pathogen-like proteins, the adaptive immune system can be primed to react to as many foreign amino acid patterns as possible, given resource and specificity constraints. Such exposure can be achieved through vaccines, which have been used for many years to cause acquired immunity against specific diseases.
Pathogen evolution typically converges to a balance between avoiding detection and preserving functionality. As the immune system has a localized effect on the pathogen's genome, the evolution will be different in different hosts and different in different parts of the pathogen's proteins. With traditional approaches to designing vaccines for rapidly evolving pathogens, evolution typically is modeled as a process of random site-independent mutations, wherein total mutation in a genome or an entire protein is assumed to capture evolutionary distance between a pair of sequences. However, the environment can affect disparate pieces of the genome and/or peptides in a protein differently. On the population level, this can lead to creation of several functional versions of each piece that are essentially arbitrarily combined into a whole protein. The combinatorial growth of functional forms of the protein creates an impression of immense diversity when mutation is averaged over the genome. Another deficiency with traditional approaches is the log mutation scores for sites in a sequence are summed together (or mutation probabilities are all multiplied together) to define a number corresponding to an evolutionary distance between two sequences when separate pieces commonly have different evolutionary distances. Thus, there is a need for improved techniques that facilitate vaccine assembly.